Measles outbreak in 2019: a warning for the post-COVID-19 pandemic period.

Introduction. At the end of 2019 and the year before, there was a significant spread of measles in the World Health Organization (WHO) European Region.Gap statement. Among the countries that reported, a measles outbreak was Bosnia and Herzegovina (BiH).Aim. To describe the measles outbreak in BiH (an entity of the Federation of BiH, FBiH) in 2019.Methodology. Confirmatory IgM serology, measles nucleic acid detection by real-time RT-PCR and virus genotyping were done in the WHO-accredited laboratory for measles and rubella at the Clinical Center of the University of Sarajevo, Unit for Clinical Microbiology. Genotype was determined in all measles-RNA-positive cases by sequence analysis of the 450 nt fragment coding the C-terminal of measles virus nucleoprotein (N).Results. From 1 January to 31 December 2019, 1332 measles cases were reported, with the peak observed in April 2019 (413/1332, 31.01 %). Sarajevo Canton had the highest incidence, number of cases and percentage (206.4; 868/1332; 65.17 %) of measles cases. Around four-fifths of infected persons were unvaccinated (1086/1332, 81.53 %), while 4.58 % of the patients (61/1332) were immunized with one dose of measles-containing vaccine. The highest proportion of cases was found in children 0-6 years of age (738/1332, 55.41 %). Measles IgM positivity was determined in 75.88 % (346/456), while virus RNA was detected in 82.46 % (47/57) of the swab samples. All measles virus sequences belonged to genotype B3. SNP (position 216: C=>T) was detected in 1 of the 40 sequences obtained during this outbreak.Conclusion. Due to suboptimal immunization coverage, BiH belongs to countries at a high risk for measles outbreaks. Post-COVID-19 (coronavirus disease 2019) pandemic, targeted and tailored strategies are required to ensure routine vaccination demand and acceptance and broad partner and stakeholder group participation.

Spatial distribution and determinants of measles vaccination dropout among under-five children in Ethiopia: A spatial and multilevel analysis of 2019 Ethiopian demographic and health survey.

BACKGROUND: Each year, vaccine-preventable diseases cost the lives of 8.8 million under-five children. Although vaccination prevents 1-2 million childhood deaths worldwide, measles vaccination dropouts are not well studied in developing countries, particularly in Ethiopia. Therefore, this study aims to assess the spatial distribution of the measles vaccination dropout and its determinants among under-five children in Ethiopia. METHODS: Data from Ethiopian Demographic and Health Survey 2019 was used for data analysis. The study used a total of 5,753 children. Spatial autocorrelations was used to determine the spatial dependency of measles vaccination dropout. Ordinary interpolation was employed to forecast measles vaccination dropout. Factors associated with measles vaccination dropout were declared significant at p-values <0.05. The data were interpreted using the confidence interval and adjusted odds ratio. A model with the lowest deviance and highest logliklihood ratio was selected as the best-fit model. RESULTS: In Ethiopia, one in three under-five children had measles vaccination dropouts. Factors such as birth interval (AOR = 1.87, 95% CI: 1.30, 2.70), unmarried marital status women (AOR = 3.98, 95% CI: 1.08, 8.45), ≤1 number of under-five children (AOR = 3.86, 95% CI: 2.56, 5.81), rural place of residence (AOR = 2.43, 95% CI: 2.29, 3.11), low community-level ANC utilization (AOR = 3.20, 95% CI: 2.53, 3.56), and residing in Benishangul Gumuz (AOR = 1.80, 95% CI: 1.061, 3.06) had higher odds of measles vaccination dropout. CONCLUSIONS: Measles vaccination dropout rates in Ethiopia among under-five children were high compared to the maximum tolerable vaccination dropout level of 10% by the WHO. Both individual and community-level variables were determinants of measles vaccination dropout. The ministry of health in Ethiopia should give attention to those mothers of under-five children who reported underutilization of ANC services and rural residences while designing policies and strategies in areas of high spatial clustering of vaccine dropout in Ethiopia.

Economic evaluation of second measles containing vaccine (MCV) dose: a systematic review of available evidence.

INTRODUCTION: The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second measles-containing vaccine (MCV2) is crucial. This study reviewed the evidence and quality of economic evaluation studies to guide MCV2 introduction. METHODS: The systematic review of model-based economic evaluation studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 2231 articles, with 876 duplicates removed and 1355 articles screened, with nine studies included for final analysis. RESULTS: Six studies reported a positive benefit-cost ratio with one resulting in net savings of $11.6 billion, and two studies estimated a 2-dose MMR vaccination program would save $119.24 to prevent one measles case, and a second dose could prevent 9,200 cases at 18 months, saving $548.19 per case. The most sensitive variables were the discount rate and vaccination administration cost. CONCLUSIONS: Two MCV doses or a second opportunity with an additional dose of MCV were highly cost-beneficial and resulted in substantial cost savings compared to a single routine vaccine. But further research using high-quality model-based health economic evaluation studies of MCV2 should be made available to decision-makers. PROSPERO REGISTRATION: CRD42020200669.

Dynamics of measles immunity from birth and following vaccination.

Measles remains a major threat to human health despite widespread vaccination. While we know that maternal antibodies can impair vaccine-induced immunity, the relative contributions of pre-existing immunity levels, maternal and infant characteristics on vaccine responses remain unclear, hampering evidence-based vaccination policy development. Here we combine serological data from 1,505 individuals (aged 0-12 years) in a mother-infant cohort and in a child cohort with empirical models to reconstruct antibody trajectories from birth. We show that while highly heterogeneous across a population, measles antibody evolution is strongly predictive from birth at the individual level, including following vaccination. Further, we find that caesarean section births were linked with 2.56 (95% confidence interval: 1.06-6.37) increased odds of primary vaccine failure, highlighting the long-term immunological consequences of birth route. Finally, we use our new understanding of antibody evolution to critically assess the population-level consequences of different vaccination schedules, the results of which will allow country-level evaluations of vaccine policy.

Persistence and heterogeneity of the effects of educating mothers to improve child immunisation uptake: Experimental evidence from Uttar Pradesh in India.

Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a substantial proportion of children remain unvaccinated. We revisit households 30 months after a randomised experiment of a health information intervention designed to educate mothers on the benefits of child vaccination in Uttar Pradesh, India. We find that the large short-term effects on the uptake of diphtheria-pertussis-tetanus and measles vaccination were sustained at 30 months, suggesting the intervention did not simply bring forward vaccinations. We apply causal forests and find that the intervention increased vaccination uptake, but that there was substantial variation in the magnitude of the estimated effects. We conclude that characterising those who benefited most and conversely those who benefited least provides policy-makers with insights on how the intervention worked, and how the targeting of households could be improved.

Effect of postpartum family planning intervention and associated factors during child immunization in Addis Ababa, Ethiopia.

Introduction: World Health Organization (WHO) recommends postpartum family planning (PPFP) as a critical component of health care that has the potential to save millions of maternal and infant lives in low- and middle-income countries. Methods: participants in our randomized, controlled trial were mothers coming for vaccination of their child in three selected health centers in Addis Ababa during the first 10 weeks postpartum. Eligible mothers were randomly assigned to intervention (pamphlet-supported counseling about the benefits of family planning) and non-intervention (routine care) arms. Data were collected when mothers came with their infants for a routine measles vaccination at nine months of life. Family planning (FP) use was compared between the groups using logistic regression, and bivariate and multivariate analyses. The study also used Kaplan Meier and Cox regressions to compare the median time of PPFP use and its correlation using SPSS version 26. The research was undertaken from December 2019 to June 2021. Results: a total of 347 women (177 control, 170 intervention) enrolled in the study. Fifty-eight percent were 24-30 years old. Young age, knowledge about FP, previous use of an FP method, and being married were found to be independent predictors for PPFP use. When comparing intervention and non-intervention groups, there was no significant effect on contraceptive use (adjusted OR 0.633 [95% CI 0.385-1.040]). Conclusion: pamphlet-supported counseling of mothers in the first 10 weeks postpartum did not increase PPFP at nine months postpartum. Successful interventions will likely require holistic strategies, especially in resource-limited settings. The trial had been registered with clinicaltrials.gov (NCT04521517) on September 24, 2019.

Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies.

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

Coverage and determinants of second-dose measles vaccination among under-five children in East Africa countries: a systematic review and meta-analysis.

Background: One of the biggest breakthroughs of contemporary medicine is measles vaccination. It is essential for the total elimination of measles. Understanding the magnitude and determinants of effective second-dose measles vaccination coverage is a critical task. Accordingly, we set out to check the best available evidence of the pooled second-dose measles vaccination coverage among under-five children in East Africa. Method: We searched electronic databases such as PubMed, Google Scholar, Cochrane, and others. Two reviewers separately carried out the search of the Joanna Briggs Institute, selection of studies, critical appraisal, and data extraction. A third party was involved in resolving the disagreement among the reviewers. Seven studies included in this study, four from Ethiopia, two from Kenya, and one from Tanzania were cross-sectional and published in English language, with publication dates before 29 November 2023. Articles lacking full-text, the intended outcome, and that are not qualitative studies were excluded from the analysis. The Microsoft Excel checklist was used to extract the data and then exported to STATA 11. In addition, I2, Funnel plots, and Egger's test were employed to measure heterogeneity and detect publication bias, respectively. A random effect model was used. Result: The meta-analysis includes a total sample size of 4,962 children from seven articles. The pooled prevalence of second-dose measles vaccination among under-five children in East Africa was found to be 32.22% [95% CI; (18.82, 45.63)], and the significant factors were as follows: birth order (1.72; OR = 95% CI: 1.32, 2.23), information about measles-containing second-dose vaccine (MCV 2) (7.39; OR = 95% CI: 5.21, 10.50), mother's marital status (1.47; OR = 95% CI: 1.05, 2.07), complete immunization for other vaccines (2.17; OR = 95% CI: 1.49, 3.17), and distance of vaccination site (3.31; OR = 95% CI: 2.42, 4.53). Conclusion: The current study found that pooled prevalence of second-dose measles vaccination coverage among under-five children was still very low. It was also observed that birth order, distance of the vaccination site, complete immunization for other vaccines, mother's marital status, and information about MCV were factors associated with second-dose measles vaccination. These factors imply that there is a need for countries and their partners to act urgently to secure political commitment, expand primary health service and health education, and increase vaccination coverage.

Exploring landscape of measles vaccination coverage: A step towards measles elimination goal in India.

INTRODUCTION: Measles remains a critical public health concern causing significant morbidity and mortality globally. Despite the success of measles vaccination programs, challenges persist, particularly in India. This study investigates dose-wise measles vaccination coverage and explores gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24-35 months. DATA SOURCES AND METHODOLOGY: The National Family Health Survey 2019-21 (NFHS-5) served as the data source and the study analyzed information from 43,864 children aged 24-35 months. Sociodemographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure were considered. Statistical analysis involved weighted estimates, chi-square tests, and multivariate multinomial logistic regression. RESULTS: The study revealed that challenges persist in achieving optimal measles vaccination coverage. Analysis by sociodemographic factors highlighted disparities in coverage, with variations in zero dose prevalence across states and districts. The percentage of zero-dose children was significantly higher, with 11.5% of children in India remaining to receive any measles vaccination. Factors influencing vaccine coverage include birth order, age, wealth quintile, social group, religion, residence, maternal education, place of delivery, media exposure, and mode of delivery. The findings from the spatial analysis show the clustering of zero-dose children is high in the northeastern states of India. DISCUSSION: Measles zero-dose children pose a significant obstacle to achieving elimination goals. Spatial analysis identifies clusters of unvaccinated populations guiding targeted interventions. The study aligns with global initiatives such as the Immunization Agenda 2030 emphasizing equitable vaccine access and discusses how India can tailor its strategies to achieve the goal. Lessons from polio eradication efforts inform strategies for measles elimination, stressing the importance of high-quality data and surveillance. The study underscores the urgency of addressing last-mile measles vaccination gaps in India. Spatially targeted interventions informed by sociodemographic factors can enhance immunization coverage. Achieving measles elimination requires sustained efforts and leveraging lessons from successful vaccination campaigns. The study findings have the potential to contribute to informed decision-making, supporting India's roadmap for the measles and rubella elimination goal.

A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Measles Outbreak Associated with a Migrant Shelter - Chicago, Illinois, February-May 2024.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents. CDPH immediately instituted outbreak investigation and response activities in collaboration with state and local health departments, health care facilities, city agencies, and shelters. On March 8, CDPH implemented active case-finding and coordinated a mass vaccination campaign at the affected shelter (shelter A), including vaccinating 882 residents and verifying previous vaccination for 784 residents over 3 days. These activities resulted in 93% measles vaccination coverage (defined as receipt of ≥1 recorded measles vaccine dose) by March 11. By May 13, a total of 57 confirmed measles cases associated with residing in or having contact with persons from shelter A had been reported. Most cases (41; 72%) were among persons who did not have documentation of measles vaccination and were considered unvaccinated. In addition, 16 cases of measles occurred among persons who had received ≥1 measles vaccine dose ≥21 days before first known exposure. This outbreak underscores the need to ensure high vaccination coverage among communities residing in congregate settings.